Abstract: Objective To explore the effects and the possible mechanisms of honokiol（HNK） on Wnt and β-catenin signaling pathway and arteriosclerosis in both vitro and vivo arteriosclerosis model. Methods In animal experiments, eight Sprague Dawley（SD） rats were used as control group, and twenty-four high-fat-chow-fed SD rats（to establish atherosclerosis rats model） were randomly divided into 3 groups: AS group（atherosclerosis model induced by high fat diet and vitamin D₂ injected）, AS+HNK group intervention with honokiol 5 mg/（kg·d） for eight weeks and AS+HNK-PNU group intervention with honokiol 5 mg/（kg·d） plus PNU-74654 100 mg/（kg·d） for eight weeks. Blood lipid levels were detected. Media cross-sectional area and wall thickness of thoracic aorta were measured by HE staining. Wnt and β-catenin protein levels were detected by Western blot. For in vitro experiments, human umbilical vein endothelial cells（HUVEC） and human aortic vascular smooth muscle cells（HA-VSMC） were cultured, and both were divided into four groups: normal control group, AS group induced by 20 mg/L oxidized low density lipoprotein（ox-LDL） for 48 hours, AS+HNK group intervention with honokiol 32 μmol/L for 48 hours and AS+HNK-PNU group intervention with honokiol 32 μmol/L plus 50 μmol/L PNU-74654 for 48 hours. Real time fluorescence quantitative polymerase chain reaction（RT-PCR） and Western blot were used to detect the mRNA and protein level of Wnt and β-catenin in cells after intervention. Transwell assay was used to detect cell migration. Results Compared with control group, triglyceride, total cholesterol and low-density lipoprotein cholesterol（LDL-C） levels increased in AS group. Blood lipid levels decreased in AS+HNK group and AS+HNK-PNU group compared with AS group. Compared with control group, media cross-sectional area and wall thickness, Wnt and β-catenin protein levels of thoracic aorta increased in AS group. Honokiol reduced media cross-sectional area, wall thickness and Wnt and β-catenin protein levels of thoracic aorta in AS model, which can be partially blocked by PNU-74654（P＜0.05）. In vitro experiments, the mRNA and protein level of Wnt and β-catenin increased by ox-LDL in HUVEC and HA-VCMS cells（P＜0.05）. The mRNA and protein level of Wnt and β-catenin in AS+HNK group deceased compared with AS group and AS+HNK-PNU gorup. Compared with control group, the migration of VSMC in AS group increased. The migration of VSMC in AS+HNK group and AS+HNK-PNU group decreased compared with AS group（P＜0.05）. Conclusions Honokiol decreases Wnt and β-catenin level, suppresses VSMC migration and ameliorates atherosclerosis in AS model. The mechanism of anti-atherosclerosis by honokiol can be mediated in part by Wnt/β-catenin signaling pathway.